Phase II study of weekly cisplatin, etoposide and irinotecan (PE/CPT) for refractory relapsed small cell lung cancer (SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7088-7088 ◽  
Author(s):  
Y. Kim ◽  
K. Goto ◽  
Y. Nishiwaki ◽  
K. Kubota ◽  
H. Omatsu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Phase Ii Trials ◽  
Organ Function ◽  
First Line Therapy ◽  
Adequate Organ Function ◽  
Grade 3 ◽  
Weekly Cisplatin

7088 Background: There is no standard treatment for relapsed SCLC. Irinotecan and etoposide has been studied in several phase II trials as active agents for relapsed SCLC. We reported the efficacy and tolerability of irinotecan combined with weekly cisplatin and etoposide (PE) in patients (pts) with sensitive relapsed SCLC (Goto, et al. Br J Cancer 2005). Methods: We conducted a phase II study to evaluate the efficacy and toxicity of PE/CPT regimen in pts with refractory relapsed SCLC, who had relapsed within 8 weeks after completion of first-line therapy. Pts must have measurable or assessable disease, age of 75 years or younger, performance status of 0 to 2 (ECOG), and adequate organ function. PE/CPT regimen consisted of cisplatin 25 mg/m2 on day 1 at one-week intervals for 9 weeks (at least 6 weeks), etoposide 60 mg/m2 on days 1–3 on week 1, 3, 5, 7, 9 (at least on week 1, 3, 5), and irinotecan 90 mg/m2 on day 1 on weeks 2, 4, 6, 8 (at least on week 2, 4, 6). After day 1 on week 2, G-CSF was administered on days when cytotoxic drugs were not given. Results: From May 2000 to January 2005, 30 pts were enrolled in this study. Pt characteristics were median age 64 years (range 44–75); 23 male and 7 female; 3 LD and 27 ED. Prior chemotherapy included PE in 13 pts, cisplatin and irinotecan in 7, carboplatin and etoposide in 5, and others in 5. 23 pts (77%) completed 6 or more weeks of chemotherapy. 2 CR and 19 PR were observed and the overall response rate was 70% (95% CI 50.6–85.3%). Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 60%, 73% and 47%, respectively. Grade 3/4 diarrhea was observed in only 7%. Coclusions: PE/CPT regimen was active and well tolerated for refractory relapsed SCLC. No significant financial relationships to disclose.

Phase II study of PX-866 in recurrent glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2053-2053 ◽  
Author(s):  
Marshall W. Pitz ◽  
Elizabeth A. Eisenhauer ◽  
Mary Valeria MacNeil ◽  
Brian Thiessen ◽  
David R. Macdonald ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stable Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Recurrent Glioblastoma ◽  
Pik3ca Mutations ◽  
Overall Response ◽  
Grade 3

2053 Background: Glioblastoma (GBM) is the most aggressive malignancy of the central nervous system. The majority have genetic changes that increase the activity of the phosphatidylinositol-3-OH kinase (PI3K) signal transduction pathway, critical for cell motility, proliferation, and survival. We present the results of PX-866, an oral PI3K inhibitor, in patients (pts) with recurrent GBM. Methods: A multinomial design of response and early progression (< 8 weeks on study) was used. In stage 1 (15 pts), 0 responses and ≥ 10 early progressions would stop accrual; after full accrual, ≥ 4 responses OR ≤ 13 early progressions was prespecified as of interest. Pts with histologically confirmed GBM, at first recurrence after chemoradiation and adjuvant temozolomide were given PX-866 8 mg daily on this single-arm phase II study. MRI and clinical exam were done every cycle (8 weeks). Tumour tissue was collected for analysis of potential markers of PI3K inhibitory activity (PTEN, EGFRviii, PIK3CA mutations). Results: A total of 33 pts were enrolled, eligible and evaluable. Median age was 56 (range 35-78), 12 were female; 29 had performance status (PS) 0-1 and 4 had PS 2. Median time from initial diagnosis to enrolment was 308 days (range 141-1256). Median number of cycles was 1 (range 1-7). Thirty-two pts have discontinued therapy, 26 due to disease/symptomatic progression and 6 due to toxicity (5 LFT elevation and 1 allergic reaction). Other adverse effects (AE): fatigue (16 pts/2 grade 3), diarrhea (11 pts/5 grade 3), nausea (19 pts/1 grade 3), vomiting (11 pts/1 grade 3) and lymphopenia (29 pts/7 grade 3/4). Five pts had related serious AEs (1 LFTs, 1 GI and 3 venous thromboembolism) All pts were evaluable for response; 25 had a best response of progression, 1 had partial response (overall response rate 3%) and seven (21%) had stable disease (SD, median 7.3 months; range 3.1-13.6). Six month PFS was 17%. In preliminary analyses, no statistical association was found between SD and PTEN or EGFRviii status (results pending in 16 pts). Conclusions: PX-866 was relatively well tolerated. Overall response rate was low, and the study did not meet its primary endpoint; however, 21% of pts obtained durable stable disease. Further correlative work is required to identify the predictor of this effect. Clinical trial information: NCT01259869.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

Multidisciplinary Approach to Brain Metastasis from Melanoma: The Emerging Role of Systemic Therapies

2013 ◽  
pp. 393-398 ◽  
Author(s):  
Georgina V. Long ◽  
Kim A. Margolin
Keyword(s):  
Brain Metastasis ◽  
Brain Metastases ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Local Therapy ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
First Line Therapy ◽  
Melanoma Brain Metastases

Melanoma brain metastases are common, difficult to treat, and carry a poor prognosis. Until recently, systemic therapy was ineffective. Local therapy (including surgery, stereotactic radiotherapy, and whole brain radiotherapy) was considered the only option for a chance of disease control in the brain, and was highly dependent on the patient's performance status and age, number and size of brain metastases, and the presence of extracranial metastases. Since 2010, three drugs have demonstrated activity in progressing or “active” brain metastases including the anti-CTLA4 antibody ipilimumab (phase II study of 72 patients), and the BRAF inhibitors dabrafenib (phase II study of 172 patients, both previously treated and untreated brain metastases) and vemurafenib (a pilot study of 24 patients with heavily pretreated brain metastases). The challenge and unanswered question for clinicians is how to sequence all the available therapies, both local and systemic, to optimize the patient's quality of life and survival. This is an area of intense clinical research. The treatment of patients with melanoma brain metastases should be discussed by a multidisciplinary team of melanoma experts including a neurosurgeon, medical oncologist, and radiation oncologist. Important clinical features that help determine appropriate first line therapy include single compared with solitary brain metastasis, resectablity, BRAF mutation status of melanoma, rate of progression/performance status, and the presence of extracranial disease.

Pemetrexed (MTA) and carboplatin (CBDCA) in the treatment of advanced pleural mesothelioma (MPM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7093-7093 ◽  
Author(s):  
B. Castagneto ◽  
M. Mencoboni ◽  
D. Degiovanni ◽  
A. Muzio ◽  
L. Giaretto ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Entire Group ◽  
Hematologic Toxicity ◽  
First Line ◽  
Ecog Performance Status ◽  
Grade 3

7093 Background: Aim of this study was to evaluate the activity and toxicity of MTA and CBDCA combination as first line chemotherapy in advanced MPM. Methods: Chemonaive patients (pts) with histologically proven, an ECOG performance status (PS) 0–2, and measurable advanced MPM were considered. The schedule of administration was: pemetrexed 500 mg/m2 in combination with CBDA AUC 5, once every 21 days for 8 cycles. Results: From July 2003 to March 2005 76 pts (54 male and 22 female) have been treated with this combination chemotherapy. Median age was 62.7 years (range 40–70); median PS 0 (range 0–3); epithelial histologic findings were in 57 (75%), mixed in 13 (17.1%), sarcomatous in 3 (3.9%), and unspecified in 3 (3.9%) pts. A total of 537 cycles was administered (median 7, range 1 to 13). Grade 3 hematologic toxicity according to WHO criteria was seen in 43 (56.6%) pts (neutropenia in 30, thrombocytopenia in 8, and anemia in 5); grade 4 hematologic toxicity in 5 (6.6%) pts. The most common nonhematologic events were grade 3 nausea/vomiting in 10 (13.1%), and fever in 4 (5.3%) pts. 74 pts were evaluable for clinical response. There were 16 (21.%) partial responses (PR) and 3 (3.9%) complete responses (CR), for an overall response rate of 23.9%. 29 (38.2%) pts reported stable disease (SD). The overall survival was considered from date of diagnosis to date of death from any cause or to date of last follow-up. The median survival time for the entire group was estimated at 23 months. Conclusions: The results of this phase II study indicate that, at this dose and schedule, the combination of CBDCA and MTA is moderately active and that the profile of toxicity is acceptable in pts with advanced MPM. No significant financial relationships to disclose.

Phase II study of TS-1 (S) plus cisplatin (P) with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18070-18070
Author(s):  
F. Ohyanagi ◽  
N. Yamamoto ◽  
A. Horiike ◽  
T. Horai ◽  
K. Gomi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Fourth Generation ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

18070 Background: Although combined chemoradiotherapy is the standard of care in stage III NSCLC, the optimal chemotherapy regimen is not established. S-1, a fourth-generation oral fluoropyrimidine is an active new agent for NSCLC and the combination with cisplatin has a favorable toxicity profile. The objective of this study was to evaluate feasibility and efficacy of S plus P with concurrent radiation for unresectable stage III NSCLC. Methods: Patients with histologically or cytologically confirmed NSCLC, 20 to 75 years in age, performance status 0–1, with no prior chemotherapy were eligible for the study. Patients were treated with P (60 mg/m2 on day 1) and S (orally at 40 mg/m2/dose bid (80 mg/m2/d), on days 1 to 14) repeated every 3–4 weeks for 4 cycles and TRT (60 Gy/30 fr over 6 weeks starting on day 2). The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 28 patients (Simon’s two-stage minimax design, P0=70%, P1=90%, a =0.1, β = 0.1). Results: Of 28 patients enrolled between August 2005 and October 2006, 28 were evaluable. There were 24 males and 4 females, median age of 63 (range 40–74) and 11 IIIA and 17 IIIB. Chemoradiotherapy was well tolerated; 2 cycles of SP and 60 Gy of TRT were administered in all patients and 24 (86%) patients received 4 cycles of SP. During concurrent chemoradiotherapy, grade 3 toxicities were neutropenia (8 pts), leukopenia (6 pts), fatigue (6 pts), anorexia (5 pts), febrile neutropenia (4 pts) and, esophagitis (4 pts). Only one grade 4 leukopenia were observed. During consolidation therapy, grade 3–4 neutropenia, anemia, esophagitis, and pneumonitis were developed in 4, 1, 1 and 2 patients, respectively. No toxic deaths have occurred. Overall RR was 85.7% (95% CI: 79.1- 98.7%) with 4 SDs and 24 PRs. The median progression-free survival and median survival is not mature enough to estimate as only 4 progression and no deaths have occurred. Conclusions: This chemoradiotherapy regimen produced promising response rate in patients with stage III NSCLC and it seems to be well-tolerated. No significant financial relationships to disclose.

A randomized, double-blind phase II trial of docetaxel plus prednisone (DP) combined with either AT101 or placebo for the first-line therapy of metastatic castration-resistant prostate cancer (CRPC).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 125-125
Author(s):  
G. Sonpavde ◽  
V. B. Matveev ◽  
J. M. Burke ◽  
J. R. Caton ◽  
M. T. Fleming ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
First Line Therapy ◽  
Castration Resistant ◽  
Risk Patients ◽  
Grade 3 ◽  
And Performance

125 Background: AT-101 (A), a small molecule oral inhibitor of the Bcl-2 protein family has broad preclinical activity including synergy with docetaxel (D). AT-101 has demonstrated activity alone and in combination with D in D-refractory patients with metastatic CRPC. Methods: A randomized, double-blind, placebo-controlled phase II trial was conducted to compare the combination of DP with either A or placebo in chemo-naive men with progressive metastatic CRPC. A key requirement was progression (bone scan, RECIST or rising PSA ≥ 2 ng/mL) despite androgen deprivation. Stratification factors were pain and performance status. Patients received DP (75mg/m2 day 1; 5mg PO b.i.d.) Q 21 days (1 cycle) with either A (40 mg b.i.d.) or placebo PO on days 1–3. Radiological assessments were performed every 3 cycles. Primary endpoint was overall survival (OS) and 221 patients were planned for 110 events (80% power, HR 0.67, 1-sided alpha 0.1). Results: 221 patients were randomized to ADP or placebo-DP and baseline factors were balanced. Efficacy outcomes (OS, PFS, PSA declines, disease control) were not significantly different ( Table ). In a subgroup of patients with poor-risk CRPC (n=34), efficacy endpoints appeared to favor ADP with a median OS of 19 months vs.14 months for placebo-DP. Grade 3/4 AEs that occurred with higher incidence in the ADP arm compared to placebo-DP included cardiac AEs (5% vs. 2%), lymphopenia (23% vs. 16%), neutropenia (47% vs. 40%), ileus (2% vs. 0%) and pulmonary embolism (6% vs. 2%). Conclusions: The combination of AT-101 with DP in men with chemonaive metastatic CRPC was well tolerated but did not extend OS compared to placebo-DP. There was a potential benefit in a subset of high-risk patients. [Table: see text] [Table: see text]

Effect of short-duration chemoimmunotherapy plus radioimmunotherapy on response rates in relapsed follicular lymphoma: A U.K. NCRI Lymphoma Group Study, CR UK/07/038.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8056-8056
Author(s):  
Timothy M Illidge ◽  
Andrew T. Bates ◽  
Andrew John Davies ◽  
Ruth Pettengell ◽  
Barry Andrews ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Median Duration ◽  
Overall Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
First Line ◽  
Ibritumomab Tiuxetan ◽  
Ecog Performance Status ◽  
Grade 3 ◽  
Kidney Liver

8056 Background: Radioimmunotherapy (RIT) and rituximab (R) maintenance have been investigated after chemotherapy (CT) or R-CT in first line treatment of follicular lymphoma (FL), but less is known about the efficacy of RIT after R-CT in relapsed FL. This phase II study was conducted to examine efficacy and safety of abbreviated R-CT followed by 90Y Ibritumomab tiuxetan in patients with recurrent FL. Methods: Patients (pts) had FL, at 1st or 2nd relapse after response to R-CT or CT alone. All had WHO/ECOG performance status ≤2, and adequate bone marrow (BM), kidney, liver and cardiac function. BM involvement by lymphoma had to be <25% prior to infusion of 90Y Ibritumomab tiuxetan, but could be higher at study entry. Pts received 3 cycles of either R-CHOP or R-CVP, followed by 90Y Ibritumomab tiuxetan (15MBq/Kg, maximum 1200 MBq). No maintenance R was given. Results: 52 pts were enrolled from 6/2008 to 7/2010. Median age was 62 years (range 31-87). 46% had high FLIPI score at entry, 31% intermediate. 80% were at 1st recurrence. Median duration of best prior remission was 27.7 months. 65% pts had previously received R and 25% doxorubicin. 71% pts had R-CHOP and 29% R-CVP, prior to RIT. Overall response rate (ORR) after 3 cycles R-CT was 94% (CR/CRu 10%) and after RIT ORR 96% (CR/CRu 28%). Grade 3/4 thrombocytopenia occurred in 58% pts (median duration 16 days): 3/52 pts after R-CT and 27/52 after RIT. Grade 3/4 neutropenia occurred in 62% pts: 15/52 pts after R-CT and 27/52 after RIT. 5 pts had a total 8 grade 3 infections, only 1 attributable to RIT. 6 pts required platelets and 4 red cell transfusions. 1 pt developed myelodysplasia 10 months after 90Y Ibritumomab tiuxetan, but no other second malignancy was recorded. PFS was 31.4 months (95% CI 15.8 - not reached). There was no difference in PFS according to FLIPI score at entry or reinduction CT (R-CHOP vs R-CVP). Pts with CR/CRu following RIT showed a trend to improved PFS compared to those with PR (12 month PFS 90% versus 63%, p=0.06). Conclusions: Abbreviated R-CT and consolidation with 90Y Ibritumomab tiuxetan is an option for pts with recurrent FL, with responses of comparable duration to those seen after a full course R-CHOP.

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Phase II study of omacetaxine (OM) and low-dose AraC (LDAC) in older patients with acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6592-6592
Author(s):  
Tapan M. Kadia ◽  
Elias Jabbour ◽  
Naveen Pemmaraju ◽  
Stefan Faderl ◽  
Gautam Borthakur ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Early Mortality ◽  
Myelogenous Leukemia ◽  
Serious Adverse Events ◽  
Acute Myelogenous ◽  
Secondary Endpoints ◽  
Adequate Organ Function ◽  
Grade 3

6592 Background: Treatment of AML in patients (pts) > 70 yrs of age with intensive chemotherapy is associated with high rates of early mortality and little benefit. Newer, lower-intensity approaches with novel mechanisms are needed. OM is a semisynthetic plant alkaloid which has demonstrated activity in AML as a single agent and with chemotherapy. Methods: We studied a low intensity program combining subcutaneous (SQ) OM with SQ LDAC in pts >/= 60 yrs, with AML or MDS, a performance status (PS) of </=2, and adequate organ function. Initially, 6 pts were enrolled at the following doses: OM 1.25 mg/m2 SQ Q12 hrs x 3 days with AraC 20 mg SQ Q12 hrs x 7 days on a 4 week cycle. If safety is confirmed, the phase II portion would commence at the safe dose levels. Up to 12 courses can be given. The primary endpoint was to determine the complete remission (CR) rate. Secondary endpoints were: CR duration, DFS, OS, safety, and early mortality. Results: 17 pts were enrolled on study so far. The median age was 74 yrs (range, 64-81); the median PS was 1 (0-1). The karyotypes in these pts were: diploid in 6 (35%), complex with chromosome (chr) 5 and/or 7 abnormality (abnl) in 4 (24%), complex without chr 5 and/or 7 abnl in 2 (12%), 11q abnl in 1 (6%), poor metaphases in 1 (6%), and other in 3 (18%). Four pts with prior MDS were treated with a median of 2 prior therapies (1-3). Median bone marrow blast % at the start of therapy was 40 (15-87). The median WBC, hemoglobin, and platelets were 2.1 (0.4–24.8), 8.9 (7.7–10.7), and 45 (14–104), respectively. These pts have received a median of 1 (1-3) cycle of therapy. Of the 11 pts evaluable for response, there were 2(18%) CR, 1(9%) CRp, 1(9%) PR for an ORR of 4/11 (36%). Five pts had no response and were taken off study. Two pts died on study: 1 on day 6 and 1 on day 27. Both pts were 74 yrs with a complex karyotype. One died of pneumonia and multi-organ failure and the 2nd died from cardiac arrest. Other than the deaths, serious adverse events included grade 3 transaminitis in 1 and grade 3 heart failure in 1. Conclusions: OM and LDAC appears to be tolerable in older pts with AML. The combination appears to have activity. Stopping boundaries for futility and safety have not been breached. Enrollment is ongoing.

Activity and safety of CPBev regimen (cisplatinum, pemetrexed, and bevacizumab) as first-line therapy for locally advanced or metastatic adenocarcinoma of the lung: Final results of a phase II study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18026-e18026
Author(s):  
Roberto Bordonaro ◽  
Hector Soto-parra ◽  
Carmelo Giannitto-Giorgio ◽  
Saverio Cinieri ◽  
Fiorenza Latteri ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Statistical Design ◽  
Vitamin Supplementation ◽  
Advanced Lung Cancer ◽  
First Line Therapy ◽  
Grade 3

e18026 Background: During the past five years the paradigms of advanced lung cancer therapy dramatically changed; Bevacizumab and Pemetrexed, when administered separately in association with platinum salts, demonstrated to improve survival in patients with non-squamous histologies. In the aim to investigate activity and safety of a three-drugs-regimen containing both these agents and cis-platinum, we conducted a multi-institutional phase II study started on november 2007. Methods: chemonaive patients with non-squamous non-small cell lung cancer were considered eligible We adopt the two-stage of Simon model as statistical design of the study; activity of the regime, expressed as overall response rate and safety were the main end-points. Administered doses were 75 and 500 mg/p.s.m for cis-platinum and pemetrexed respectively and 7.5 mg./kg for Bevacizumab, for 3 - 6 cycles. G-CSF were administered only after the first cycle of therapy, whereas vitamin supplementation started from day 1 of the first cycle. No maintenance therapy was allowed. Results: We registered 9 partial responses among the first 15 patients treated so, accordingly with the design of the study, we completed the enrollment up to 32 patients. Patients characteristics are: male/female: 20/12, median age (years): 59 (r. 36 - 77), ECOG-WHO/PS 0/1: 21/11. One hundred eighty-three cycles of CPBev were administered: we registered only 13 cases of grade 3 adverse events. No grade 4 toxicities were observed. One case of allergic reaction to cis-platinum were observed. In terms of response rate, we registered 20/32 (62.5%) partial responses, 8/32 (25%) stable diseases and 4/32 (12.5%) progressive diseases, with a clinical benefit rate of 28/32 (87.5%). Results in terms of outcome parameters expressed by progression-free and overall survival will be presented at the meeting. Conclusions: On the basis of our data, CPBev have a good toxicity profile and seems to be extremely active in advanced non-squamous lung carcinomas.

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